Fracture Risk in Men With Thyroid Cancer

In a cohort of male veterans, osteoporosis was more common in those with thyroid cancer, according to the results of a study published in The Oncologist. Fractures, however, were not. 

“Serum TSH [thyroid-stimulation hormone] was not associated with fracture. The [investigators] only found a difference in the incidence of osteoporosis. I find that very interesting because, in theory, the reason you don’t want to suppress someone so much is that you don’t want them to fracture as this is the negative clinical impact of osteoporosis,” said Jennifer M. Perkins, MD, MBA, Associate Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Duke University, Durham, in an exclusive interview with Cancer Network.

In the current retrospective case-control study, researchers mined the Veterans Health Administration Corporate Data Warehouse (2004–2013) for 10,370 patients (83.8% men) with thyroid cancer vs. 10,370 controls (83.8% men) matched by age, sex, weight, and steroid use. A mixed-effects regression model was employed to compare the groups for osteoporosis and fracture risk. On subgroup analysis, thyroid cancer patients were examined for the effect of thyroid hormone on these factors.

Osteoporosis was more common in thyroid cancer patients (7.3% vs. 5.3%; OR, 1.33; 95% CI, 1.18-1.49) when controlling for covariates. In the subgroup of thyroid cancer patients, lower TSH (OR, 0.93; 95% CI, 0.90–0.97); female sex (OR, 4.24; 95% CI, 3.53–5.10); older age (e.g., ≥85 years: OR, 17.18; 95% CI, 11.12–26.54 vs. <50 years); and androgen use (OR, 1.63; 95% CI, 1.18–2.23) were all correlated with osteoporosis. Serum TSH, however, was not significantly linked to fractures (OR, 1.01; 95% CI, 0.96–1.07).

Hypotheses reflecting how TSH suppression may result in bone loss include a direct effect on bone formation and bone resorption mediated by the TSH receptor on osteoblast and osteoclast precursors.

The authors highlighted clinical implications of the study. “Patients with thyroid cancer may be subject to increased screening with bone density scans irrespective of their overall risk for osteoporosis and fractures, leading to unnecessary increased health care use and increased costs. Also, physicians may be overestimating the effect of thyroid cancer treatments on bone health. In contrast, osteoporosis may be underdiagnosed in the population at large without thyroid cancer despite the presence of other risk factors, which in turn may lead to undertreatment and subsequent fractures.”

Historically, this line of research has faced challenges. “Previous studies exploring the link between thyroid cancer treatment and osteoporosis and fractures in men have yielded conflicting results because of heterogeneity in study design, small sample sizes, cross-sectional nature, lack of biochemical data, and varying degrees of control for confounding variables,” wrote the authors, led by Maria Papaleontiou, MD, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

Dr. Perkins noted that you wouldn’t want to suppress TSH in patients with low-risk thyroid cancer or in those who were at intermediate risk and have demonstrated an excellent biochemical response. “Articles such as this one on osteoporosis and thyroid cancer are reinforcement that we should appropriately treat patients with thyroid cancer and not suppress their TSH if it’s not needed. The take-home message is that it’s all about risk vs. benefit and less is more in most cases. You don’t want to over suppress TSH and make patients hyperthyroid who won’t benefit from it from the standpoint of risk of cancer recurrence,” she said. 

Finally, Dr. Perkins noted that she would have liked to understand the relationship between TSH ranges and osteoporosis/fracture risk in patients without thyroid cancer (ie, the controls) because that’s an important comparison.